Allostasis and Allostatic Load Implications for Neuropsychopharmacology
Abstract
The primary hormonal mediators of the stress response, glucocorticoids and catecholamines, have both protective and damaging effects on the body. In the short run, they are essential for adaptation, maintenance of homeostasis, and survival (allostasis). Yet, over longer time intervals, they exact a cost (allostatic load) that can accelerate disease processes. The concepts of allostasis and allostatic load center around the brain as interpreter and responder to environmental challenges and as a target of those challenges. In anxiety disorders, depressive illness, hostile and aggressive states, substance abuse, and post-traumatic stress disorder (PTSD), allostatic load takes the form of chemical imbalances as well as perturbations in the diurnal rhythm, and, in some cases, atrophy of brain structures. In addition, growing evidence indicates that depressive illness and hostility are both associated with cardiovascular disease (CVD) and other systemic disorders. A major risk factor for these conditions is early childhood experiences of abuse and neglect that increase allostatic load later in life and lead individuals into social isolation, hostility, depression, and conditions like extreme obesity and CVD. Animal models support the notion of lifelong influences of early experience on stress hormone reactivity. Whereas, depression and childhood abuse and neglect tend to be more prevalent in individuals at the lower end of the socioeconomic ladder, cardiovascular and other diseases follow a gradient across the full range of socioeconomic status (SES). An SES gradient is also evident for measures of allostatic load. Wide-ranging SES gradients have also been described for substance abuse and affective and anxiety disorders as a function of education. These aspects are discussed as important, emerging public health issues where the brain plays a key role.
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The HPA axis is likely to show dysregulation, potentially both hyper- and hypo-functioning, rather than only increased reactivity.
“it has become clear that a more accurate prediction is that the HPA axis will likely exhibit evidence of dysregulation and that this dysregulation may involve both hyper- and hypo-functioning”
From The Differential Impacts of Early Physical and Sexual Abuse and Internalizing Problems on Daytime Cortisol Rhythm in School-Aged Children (2010) · cites this paper as McEwen, 2000
Activation of HPA and SNS axes can be sustained after traumatic events through deficient CNS regulation and adaptation to stress, consistent with an allostatic load model of disease.
“Activation of HPA and SNS axes can be sustained after traumatic events through deficient CNS regulation and adaptation to stress, consistent with an allostatic load model of disease.(13)”
A blunted cortisol response may be a sign of physiological dysregulation and is consistent with an allostatic load model of chronic or severe stress exposure.
“Other evidence suggests that a blunted cortisol response may be a sign of physiological dysregulation and is consistent with an allostatic load model of chronic or severe stress exposure.(13)”
Chronic stress is a key mechanism explaining the association between disadvantaged social environments and adverse health outcomes.
“A key mechanism for explaining this association is chronic stress, which is believed to degrade physiological functioning (3)(4)(5)(6)”
From Social disadvantage, genetic sensitivity, and children's telomere length (2014) · cites this paper as [4]
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- Authors
- McEwen, B.
- Affiliations
- Rockefeller University (US)
- Corresponding author
- McEwen, B
- Venue
- Neuropsychopharmacology
- Published
- 2000-02
- Volume
- 22
- Issue
- 2
- Pages
- 108-124
- ISSN
- 0893-133X (ISSN-L)
- OpenAlex
- W1978762354
- Cited by
- 1,833
- References
- 32
- Citations by year
- 2026: 68 · 2025: 94 · 2024: 98 · 2023: 127 · 2022: 98 · 2021: 92 · 2020: 82 · 2019: 71 · 2018: 74 · 2017: 100 · 2016: 109 · 2015: 85 · 2014: 69 · 2013: 87 · 2012: 74
- FWCI
- 2.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- John D. and Catherine T. MacArthur Foundation
- University of California, San Francisco
- National Institute of Mental Health (MH-41256)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Social Sciences › Health › Health disparities and outcomes
- Keywords
- allostasis, allostatic load, stress response, glucocorticoids, catecholamines, anxiety disorders, depression, hostility, substance abuse, post-traumatic stress disorder, diurnal cycle, brain atrophy, cardiovascular disease, childhood abuse and neglect, socioeconomic status, social gradient
- MeSH terms
- Adaptation, Physiological, Mental Disorders, Homeostasis, Hormones, Humans, Stress, Physiological, Stress, Psychological
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